European Spine Journal

, Volume 17, Issue 11, pp 1482–1487 | Cite as

Measurement of the concentration of three antituberculosis drugs in the focus of spinal tuberculosis

Original Article
First Online:
Received:
Revised:
Accepted:

Abstract

This is an experimental study on the distribution of antituberculosis drugs such as rifampin, isoniazid, and pyrazinamide in pathologic vertebrae of spinal tuberculosis in order to provide the regimen of chemotherapy and surgical treatment of spinal tuberculosis. The distribution of antituberculosis drugs in pathologic vertebral tissues matters greatly to the clinical effect of spinal tuberculosis’ treatment. However, few pharmacokinetic studies and clinical reports about the concentrations of antituberculosis drugs in vertebral foci have been published so far. Twenty-four patients with spinal tuberculosis were divided into sclerotic group (n = 15) or non-sclerotic group (n = 9) according to radiographic features of lesion. All patients received chemotherapy with 2HRZ/2·5H2R2Z2 for a duration of 4.5 months. Four weeks after chemotherapy all patients underwent surgery and the specimen of serum, ilium, and pathologic vertebral tissues, including sclerotic wall, subnormal osseous tissue, and foci were obtained during operation in 120–130 and 180–190 min after oral intake in the morning, respectively. The levels of three drugs in the specimen were measured using HPLC method. The concentration levels of isoniazid, rifampin and pyrazinamide varied greatly in different tissues of spinal tuberculosis, of which the bactericidal concentration values of isoniazid and rifampin and fivefold minimal inhibitory concentration (MICs) of pyrazinamide were found in subnormal vertebral bone and self-contrast ilium, the MICs of all drugs were found in sclerotic wall outside foci, and undetected level was found in foci inside the sclerotic wall. To patients without vertebral sclerotic wall around the foci, the isoniazid in foci was of bactericidal level and rifampin and pyrazinamide in foci corresponded to the MICs respectively. The sclerotic bone of affected vertebra plays an important role in blocking the antituberculosis drug’s penetration into tuberculosis focus.

Keywords

Spine Tuberculosis Isoniazid Rifampicin Pyrazinamide High performance liquid 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was supported in part by grants from a grant from Ningxia Science Foundation, People’s Republic of China. The technical assistance of Dr. Wei Minji is greatly appreciated.

References

  1. 1.
    Both B (1984) Penetration of parenterally administered rifampicin into bone tissue. Chemotherapy 30:358–365Google Scholar
  2. 2.
    Coordination Group of the State Short-Course Chemotherapy for Pulmonary Tuberculosis (1998) Clinical comparison studies on a 5 month chemotherapy and 6 month whole course intermittent program in the treatment of pulmonary tuberculosis with positive bacteria. Chin J Tuberc Respir 21:388–391Google Scholar
  3. 3.
    Deng L, Jiang X, Chen J et al (2003) Study on pharmacokinetics and bioequivalent evaluation of Yif uxianan tablets. Chin Hosp Pharm J 23:475–478Google Scholar
  4. 4.
    Dept of Orthopedics (1974) Tianjin Hospital, Clinical Osteology (II). Tuberculosis, 1st edn. People’s Health Publishing House, Beijing, p. 215Google Scholar
  5. 5.
    Ge Z, Wang Z, Wei M (2004) An experimental study of rifampicin’s distribution in different tissues of spinal tuberculosis patients. Chin J Spine Spinal Cord 14:741–744Google Scholar
  6. 6.
    Jain R, Sawhney S, Berry M (1993) Computed tomography of vertebral tuberculosis: patterns of bone destruction. Clin Radiol 47:196–199PubMedCrossRefGoogle Scholar
  7. 7.
    Lee J (1997) Clinical pharmacology, 2 edn. People’s Health Publishing House, Beijing, pp 692–700Google Scholar
  8. 8.
    Li P, Yang W, Zhong Q (2003) Computed tomography of vertebral tuberculosis. CT Theory 7 Appl 13:33–35Google Scholar
  9. 9.
    Liu H, Wang J, Hou J et al (2000) Pharmacokinetics of rifampin in healthy volunteers after a high oral dose. Chin J Pharm 35:396–398Google Scholar
  10. 10.
    Panchagnula R, Sood A, Sharda N et al (1999) Determination of rifampicin and its main metabolite in plasma and urine in presence of pyrazinamide and isoniazid by HPLC method. J Pharm Biomed Anal 18:1013–1020. doi: 10.1016/S0731-7085(98)00112-5 PubMedCrossRefGoogle Scholar
  11. 11.
    Roncoroni AJ, Manuel C, Nedjar C et al (1981) Cefamandole bone diffusion in patients undergoing total hip replacement. Chemotherapy 27:166–172PubMedCrossRefGoogle Scholar
  12. 12.
    Tuli SM, Kumar K, Sen PC (1977) Penetration of antituberculosis drugs in clinical osteoarticular tubercular lesion. Acta Orthop Scand 48:362–368PubMedCrossRefGoogle Scholar
  13. 13.
    Wang Z, Ge Z, Jin W et al (2007) Treatment of spinal tuberculosis with ultrashort-course chemotherapy in conjunction with partial excision of pathologic vertebrae. Spine J 7:671–681. doi: 10.1016/j.spinee.2006.07.016 PubMedCrossRefGoogle Scholar
  14. 14.
    Wang Z, Yang W, Jin W et al (2004) Treatment of spinal tuberculosis with anterior partial vertebrectomy, iliac grafting and internal fixation. Chin J Spine Spinal Cord 14:716–719Google Scholar
  15. 15.
    Wu Q, Duan L, Ling Y et al (1998) Comparison of three antituberculous drugs in serum and cold abscessed of patients with spinal tuberculosis. Chin J Tuberc Respir 21:617–619Google Scholar
  16. 16.
    Yang W, Wang Z, Qiao Y et al (2006) Resectable range of anterior partial vertebrectomy for spinal tuberculosis. J Fourth Mil Med Univ 27:695–697Google Scholar
  17. 17.
    Zhuo H, Lei Y, Wang C et al (1999) Study of pharmacokinetic and bioavailability of a combination rifampicin tablet in healthy volunteers. Chin J Clin Pharm 15:425–430Google Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of Orthopedic SurgeryHospital of the Ningxia Medical SchoolYinchuan, NingxiaPeople’s Republic of China
  2. 2.Institute of Pharmacologic ResearchBeijing UniversityBeijingChina

Personalised recommendations